# Respiratory Physiology Core

> **NIH NIH P01** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2020 · $251,250

## Abstract

Project Summary/Abstract
The respiratory physiology core, led by a pulmonologist clinician scientist with a special interest in respiratory
physiology, performs pulmonary functional phenotyping in rodents. These measurements include awake
respiratory testing, ventilated in vivo pulmonary function measurements and broncho-alveolar lavages and
analysis. Early onset emphysema is the hallmark of alpha-1-antitrypsin deficiency (AATD) in humans and
manifests as airway obstruction and progressive respiratory failure. AAT is a protease inhibitor that neutralizes
neutrophil elastase (NE). When AAT is absent or deficient in the lungs, unopposed NE degrades and destroys
the lung parenchyma and alveolar walls. This unchecked proteolytic activity leads to emphysema.
Emphysema is the permanent enlargement of airspaces in the gas exchange region of the lungs. Clinically,
AATD patients with emphysema have decreased pulmonary function testing, airway obstruction, decreased
elastance and increased compliance. The novel AAT-KO model created here at University of Massachusetts
Medical School (UMMS) provides an ideal tool to test the physiological manifestations of pulmonary disease.
Preliminary testing reveals that this model does indeed have characteristic pulmonary findings similar to those
seen in humans. In fact, the AAT-KO mouse has markedly increased static compliance and decreased
elastance [indicative of emphysema] as well as evidence of airway obstruction. Thus, this AAT-KO model, with
these clinically relevant pulmonary manifestations, provides an ideal platform to test the novel AAV and miRNA
therapeutics proposed in this translational program project grant. Furthermore, the ability to assess the impact
on pulmonary function and mechanics allows a better understanding of the translational potential of these
therapies when they advance to clinical trials.

## Key facts

- **NIH application ID:** 9935129
- **Project number:** 5P01HL131471-05
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Mai ElMallah
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $251,250
- **Award type:** 5
- **Project period:** — → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9935129

## Citation

> US National Institutes of Health, RePORTER application 9935129, Respiratory Physiology Core (5P01HL131471-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9935129. Licensed CC0.

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